• Journal of Ginseng Research
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• v.15 no.2
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• pp.112-116
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• 1991

The metabolic fate of ginsenosides including gastrointestinat absorption, organ distribution, excretion and metabolism in liver was investigated by tracer studies using the radio-labeled ginsenosides. 3H-ginsenosides were shown to be absorbed from the mouse digestive tract and then to be excreted rapidly into urine and/or bile. Bile juice was concluded to play a significant role in absorption of ginsenosides. The total concentration of radioactivity persisted in tissues 24 hrs after oral administration was less than 1.3% of the administered dose and Rbl showed the highest value. The concentrations of radioactivity were relatively high in the liver and kidney. After administration of Rbl radioactivity was detected in the brain. After oral administration of 8H-ginsenosides, major component excreted into urine was found to be the intact ginsenosides and decomposed and/or metabolized products were found in GIT in the case of Rbl. 3H-ginsenoside Rbl was shown to be metabolized in the liver and the metabolite was suggested to be an acylated compound of Rbl by a certain organic acid.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.293-299
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• 2013

20S-dihydroprotopanaxadiol (2H-PPD) is a derivative of protopanaxadiol, a glycone of ginsenosides prepared from Panax ginseng. Although ginsenosides and acidic polysaccharides are known to be major active ingredients in ginseng, the immunopharmacological activities of their metabolites and derivatives have not been fully explored. In this study, we aimed to elucidate the regulatory action of 2H-PPD on the function of monocytes and macrophages in innate immune responses. 2H-PPD was able to boost the phagocytic uptake of fluorescein isothiocyanate-dextran in macrophages and enhance the generation of radicals (reactive oxygen species) in sodium nitroprusside-treated RAW264.7 cells. The surface levels of the costimulatory molecules such as CD80 and CD86 were also increased during 2H-PPD treatment. In addition, this compound boosted U937 cell-cell aggregation induced by CD29 and CD43 antibodies, but not by cell-extracellular matrix (fibronectin) adhesion. Similarly, the surface levels of CD29 and CD43 were increased by 2H-PPD exposure. Therefore, our results strongly suggest that 2H-PPD has the pharmacological capability to upregulate the functional role of macrophages/monocytes in innate immunity.

• Journal of Microbiology and Biotechnology
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• v.25 no.7
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• pp.1170-1176
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• 2015

Ginsenosides, the major active component of ginseng, are traditionally used to treat various diseases, including cancer, inflammation, and obesity. Among these, compound K (CK), an intestinal bacterial metabolite of the ginsenosides Rb₁, Rb₂, and Rc from Bacteroides JY-6, is reported to inhibit cancer cell growth by inducing cell-cycle arrest or cell death, including apoptosis and necrosis. However, the precise effect of CK on breast cancer cells remains unclear. MCF-7 cells were treated with CK ($0-70{\mu}M$) for 24 or 48 h. Cell proliferation and death were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Changes in downstream signaling molecules involved in cell death, including glycogen synthase kinase $3\beta$ ($GSK3\beta$), $GSK3\beta$, $\beta$-catenin, and cyclin D1, were analyzed by western blot assay. To block $GSK3\beta$ signaling, MCF-7 cells were pretreated with $GSK3\beta$ inhibitors 1 h prior to CK treatment. Cell death and the expression of $\beta$-catenin and cyclin D1 were then examined. CK dose- and time-dependently inhibited MCF-7 cell proliferation. Interestingly, CK induced programmed necrosis, but not apoptosis, via the $GSK3\beta$ signaling pathway in MCF-7 cells. CK inhibited $GSK3\beta$ phosphorylation, thereby suppressing the expression of $\beta$-catenin and cyclin D1. Our results suggest that CK induces programmed necrosis in MCF-7 breast cancer cells via the $GSK3\beta$ signaling pathway.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.799-807
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• 2020

Background: The skin acts as a barrier to protect organisms against harmful exogenous agents. Compound K (CK) is an active metabolite of ginsenoside Rb1, Rb2 and Rc, and researchers have focused on its skin protective efficacy. In this study, we hypothesized that increased expression of the serine protease inhibitor Kazal type-5 (SPINK5) may improve skin barrier function. Methods: We screened several ginsenosides to increase SPINK5 gene promoter activity using a transactivation assay and found that CK can increase SPINK5 expression. To investigate the protective effect of CK on the skin barrier, RT-PCR and Western blotting were performed to investigate the expression levels of SPINK5, kallikrein 5 (KLK5), KLK7 and PAR2 in UVB-irradiated HaCaT cells. Measurement of transepidermal water loss (TEWL) and histological changes associated with the skin barrier were performed in a UVB-irradiated mouse model and a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis-like model. Results: CK treatment increased the expression of SPINK5 and decreased the expression of its downstream genes, such as KLKs and PAR2. In the UVB-irradiated mouse model and the DNCB-induced atopic dermatitis model, CK restored increased TEWL and decreased hydration and epidermal hyperplasia. In addition, CK normalized the reduced SPINK5 expression caused by UVB or DNCB, thereby restoring the expression of the proteins involved in desquamation to a level similar to normal. Conclusions: Our data showed that CK contributes to improving skin-barrier function in UVB-irradiated and DNCB-induced atopic dermatitis-like models through SPINK5. These results suggest that therapeutic attempts with CK might be useful in treating barrier-disrupted diseases.

• Journal of Dairy Science and Biotechnology
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• v.32 no.1
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• pp.47-53
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• 2014

In this study, our aim was to investigate the changes in ginsenosides and polyphenols in red ginseng extract fermented by Lactobacillus acidophilus and to manufacture fresh cheese using fermented red ginseng extract. Red ginseng extract (3%, w/v) was fermented by L. acidophilus for 24 h. On performing lactic acid bacteria counts, we determined that L. acidophilus reached its maximum growth phase after 16 h; this was followed by decrease in growth. During fermentation, the levels of ginsenosides Rg3 (20S) and Rg3 (20R) as well as protopanaxadiol (20R), F1, and compound K increased, while those of s Rb2, Rd, Rf, and Rg1 decreased. The pH, titratable acidity, and viable cell counts in fresh cheese prepared using fermented red ginseng extract were measured during the storage period. The pH decreased over time, while titratable acidity and viable cell counts increased with increase in the duration of the storage period. Sensory tests showed that the overall sensory properties of fresh cheese prepared using 1% fermented red ginseng extract were similar to those of the control groups. This result suggests that L. acidophilus-fermented red ginseng has potential for development as a new bioactive material.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.1
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• pp.45-52
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• 2015

Objectives To check marker content for appropriate quality control of Woohwangchungsimwon sterilized to ensure microbiological safety and to observe antioxidant activity for any changes in efficacy. Methods To measure any effects of sterilization on the effective compounds, 8 ingredients of Woohwangchungsimwon were screened for any changes in marker content using HPLC-DAD. Using the colorimetric method on the microplate reader any changes in total phenolic compound and flavonoid levels were observed. Antioxidant activity was measured using the DPPH, ABTS, and FRAP. Results Of the ingredients of Woohwangchungsimwon, 8 were subject to quantitative analysis before and after sterilization. 21.6 mg and 1.93 mg of Glycyrrhizin was found in Glycyrrhiza uralensis Fischer pre and post sterilization, respectively. Decursin found in Angelica gigas Nakai increased from 0.16 mg to 0.29 mg after sterilization. Bilirubin found in Gallstone of Bostaurusvar. domesticus increased from 0.24 mg to 0.33 mg. Cinnamic acid found in Cinnamomum cassia Blume increased from 0.02 mg to 0.05 mg. Ginsenoside Rb1 found in Panax ginseng C. A. Meyer decreased from 0.02 mg to 0.14 mg. Paeoniflorin found in Paeonia lactiflora Pallas increased from 1.05 mg to 1.13 mg. Amygdalin found in Armeniacae Amarum Semen increased from 2.68 mg to 2.83 mg. L-muscone found in Musk increased from 0.63 mg to 0.76 mg. As for total phenolic compound and total flavonoid content, there was a 1.22 and 4.15-fold increase. DPPH and ABTS increased by 20.45% and 20.69%, respectively. FRAP activity was 2.78 times more active post stabilization. Conclusions This study confirmed that high temperature high pressure steam sterilization, a method used to ensure microbiological safety of Woohwangchungsimwon, does not affect marker content; in other words, does not affect quality of the Woohwangchungsimwon. It could also be seen that total phenolic compound and flavonoid content increased after sterilization. An antioxidant activity test showed that there was significantly increased activity of antioxidants.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.711-721
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• 2022

The immune system is one of the most important parts of the human body and immunomodulation is the major function of the immune system. In response to outside pathogens or high inflammation, the immune system is stimulated or suppressed. Thus, identifying effective and potent immunostimulants or immunosuppressants is critical. Ginsenosides are a type of steroid saponin derived from ginseng. Most are harmless to the body and even have tonic effects. In this review, we mainly focus on the immunostimulatory and immunosuppressive roles of two types ginsenosides: the protopanaxadiol (PPD)-type and protopanaxatriol (PPT)-type. PPT-type ginsenosides include Rg1, Rg2, Rh4, Re and notoginsenoside R1, and PPD-type ginsenosides include Rg3, Rh2, Rb1, Rb2, Rc, Rd, compound K (CK) and PPD, which activate the immune responses. In addition, Rg1 and Rg6 belong to PPT-type ginsenosides and together with Rg3, Rb1, Rd, CK show immunosuppressive properties. Current explorations of ginsenosides in immunological areas are in the preliminary stages. Therefore, this review may provide some novel ideas to researchers who study the immunoregulatory roles of ginsenosides.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.780-789
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• 2022

Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.

• Journal of Ginseng Research
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• v.29 no.1
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• pp.37-43
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• 2005

We performed in vitro and in vivo studies to know whether the inhibitory effects of ginsenosides on $5-HT_{3A}$ receptor channel acctivity are coupled to anti-nausea and anti-vomiting action. In vitro study, we investigated the effect of compound K (CK) and M4, which are ginsenoside metabolites, on human $5-HT_{3A}$ receptor channel activity expressed in Xenopus oocytes using two-electrode voltage clamp technique. Treatment of CK or M4 themselves had no effect in both oocytes injected with $H_2O\;and\;5-HT_{3A}$ receptor cRNA. In oocytes injected with $5- HT_{3A}$ receptor cRNA, M4 treatment inhibited more potently 5-HT-induced inward peak current $(I_{5-HT})$ than CK with dose-dependent and reversible manner. The half-inhibitory concentrations $(IC_{50})$ of CK and M4 were $36.9\;\pm\;10.1\;and\;7.3\;\pm\;2.2\;{\mu}M$, respectively. The inhibition of $I_{5-HT}$ by M4 was non-competitive and voltage-independent. These results indicate that M4 might regulate $5-HT_{3A}$ receptors. In vivo experiments, injection of cisplatin (7.5 mg/kg, i.v.) induced both nausea and vomiting with 1 h latency. These episodes reached to peak after 2 h and persisted for 4 h. Pre-treatment of GTS (500 mg/kg, p.o.) significantly reduced cisplatin-induced nausea and vomiting by $51\;\pm\;8.4\;and\;48.8\;\pm\;6.4\%$ during 4 h compared to GIS­untreated group, respectively. These results show the possibility that in vitro inhibition of $5-HT_{3A}$ receptor channel activity by ginsenosides might be coupled to in vivo anti-emetic activity.

• Herbal Formula Science
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• v.24 no.2
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• pp.80-99
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• 2016

Objectives : Instrumental chemical analysis was utilized to investigate the effect of Add-Omit-Saenghyeoryunbu-eum(AO-SHU) on diabetic treatment. One of the most exciting, yet also controversial, arguments is the safety and biological mechanisms of the natural medicine on human body. Therefore, the aim of this study is to provide a better understanding on bioactive chemical components, hazards of heavy metal contamination and biological mechanism of the diabetic medicine composed of 12 different natural herbs. Methods : To study bioactive compound and metallic component in the diabetic medicine in detail, LC-MS/MS (Liquid Chromatography-Mass/Mass), GC (Gas Chromatography) and ICP (Inductively Coupled Plasma) were utilized to characterize the extract of the diabetic medicine and the result was compared with 18 marker substances selected from literature survey. In addition, in vitro assay experiments including GPR 119 activity and human DGAT-1 inhibition, and OGTT (Oral Glucose Tolerance Test) were performed to verify the effectiveness of this medicine on diabetic treatment. Results : Out of 18 marker substances, 9 bioactive compounds were identified from LC-MS/MS analysis which include Citruline, Catalpol, Berberine, Ginsenoside Rb1, Ginsenoside Rg1, Oleanolic acid, β-Sitosterol, Mangiferin, and Schizandrin. ICP study on 245 residual pesticides revealed that 239 species were not detected but 6 species, Dimethomorph, Trifloxystrobin, Pyraclostrobin, Isoprocarb, Carbaryl and Flubendiamide, while the amounts are trace levels, below permitted concentrations. The biological activity was observed in vitro assay and Oral Glucose Tolerance Test(OGTT), which are consistent with a preliminary clinical test result, a drop in blood sugar level after taking this herbal medicine. Conclusions : Instrumental chemical analysis using LC-MS/MS, GC, and ICP was conducted successfully to identify bioactive compounds in AO-SHU for the treatment of diabetes, finding 9 bioactive compounds. Furthermore, in vitro assay experiments and OGTT show that AO-SHU has its biological activities, which imply that it can be a candidate for the future diabetes remedy.